The preparation or delivery of pharmaceutical drugs and medicaments as powders is demanding. Pharmaceutical applications must take careful account of various particle or powder characteristics, and pharmaceutical compositions often are prepared as powders as an intermediate step to final formulation in many forms for delivery to the patient. Pharmaceutical compositions can be tableted or encapsulated for oral gastro-intestinal ingestion and delivery. Powder pharmaceutical compositions also can be incorporated into a dry powder inhaler (DPI) for delivery to the respiratory tract. Dry powder inhalation of a pharmaceutical composition requires unique and challenging physical property profiles for a powder. For efficient and efficacious delivery to the lung in powder form, drug particles must be sufficiently small and deagglomerated. Lung deposition improves substantially for particles less than 5 microns in aerodynamic diameter and decreases substantially for particles with an aerodynamic diameter greater than 5 microns. However, below 5 microns in particle diameter, deagglomeration efficiency declines markedly.
Balancing these competing effects, in one example, has involved adsorbing small respirable drug particles onto larger inert carrier particles which provide for bulk deagglomeration but which require additional energy to release the drug from the surface of the carrier particles. Recent advances in improving the flowability characteristics of powders by adding surface-modified nanoparticles are disclosed in International Publication No. WO 2007/019229, entitled “Compositions Exhibiting Improved Flowability” (incorporated herein by reference). However, challenges remain in handling surface-modified nanoparticles and pharmaceutically active ingredients.
There is, therefore, a continuing need for methods of making pharmaceutical compositions in dry powder form.